This supplement will continue to fund our Center for Common Disease Genomics (UM1HG008853) at the McDonnell Genome Institute at Washington University entitled, ?A platform for large-scale discovery in common disease.? In the supplemental period we will continue our multi-ethnic case-control whole genome sequencing (WGS) study focused on mapping novel disease genes and variants underlying risk and protection from early- onset coronary artery disease (EOCAD). Along with EOCAD cases, we aim to select deeply phenotyped controls whenever possible in order to study the genetic basis of quantitative cardiometabolic risk factors. After completing the WGS, we will assemble a joint callset that includes all EOCAD cases and controls from our center to enable association testing between genotypes and disease outcomes. Genotypes for the primary analysis will include testing common (individual) and rare (burden) single nucleotide variants (SNVs), insertion/deletion variants (indels), and structural variants (SVs) across coding and non-coding space. In secondary analyses, we will test for association with quantitative cardiometabolic risk factor traits and will leverage differential patterns of admixture to map causal variants underlying previously mapped disease and trait associated loci. Beyond disease association studies, we will continue to collaborate with consortium members to create genomic resources that will be used by the scientific community such as aggregated site frequencies, imputation resources, and open source analysis methods.
The overarching goal of our research program is to identify new variants, genes and pathways that contribute to common human diseases. In this project, we aim to sequence and analyze many thousands of human genomes from healthy and diseased individuals to identify genetic factors conferring risk or protection from cardiovascular disease and risk factors. We also aim to create new analysis tools and data resources to enable disease gene mapping efforts in the broader scientific community.
| Regier, Allison A; Farjoun, Yossi; Larson, David E et al. (2018) Functional equivalence of genome sequencing analysis pipelines enables harmonized variant calling across human genetics projects. Nat Commun 9:4038 |
| Lin, Chien-Jung; Lin, Chieh-Yu; Stitziel, Nathan O (2018) Genetics of the extracellular matrix in aortic aneurysmal diseases. Matrix Biol 71-72:128-143 |
| Chiang, Colby; Scott, Alexandra J; Davis, Joe R et al. (2017) The impact of structural variation on human gene expression. Nat Genet 49:692-699 |
| Stitziel, Nathan O; Khera, Amit V; Wang, Xiao et al. (2017) ANGPTL3 Deficiency and Protection Against Coronary Artery Disease. J Am Coll Cardiol 69:2054-2063 |
| Stitziel, Nathan O (2017) Human genetic insights into lipoproteins and risk of cardiometabolic disease. Curr Opin Lipidol 28:113-119 |
| Auer, Paul L; Stitziel, Nathan O (2017) Genetic association studies in cardiovascular diseases: Do we have enough power? Trends Cardiovasc Med 27:397-404 |
| Ganel, Liron; Abel, Haley J; FinMetSeq Consortium et al. (2017) SVScore: an impact prediction tool for structural variation. Bioinformatics 33:1083-1085 |
